Variant rs118177681 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001036.6(RYR3):c.13365G>A(p.Glu4455Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,613,996 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0088 ( 11 hom., cov: 33)

Exomes 𝑓: 0.011 ( 131 hom. )

Consequence

RYR3
NM_001036.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.161

Variant links:

Genes affected

RYR3 (HGNC:10485): (ryanodine receptor 3) The protein encoded by this gene is a ryanodine receptor, which functions to release calcium from intracellular storage for use in many cellular processes. For example, the encoded protein is involved in skeletal muscle contraction by releasing calcium from the sarcoplasmic reticulum followed by depolarization of T-tubules. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

RYR3 links:

RYR3 (HGNC:):

RYR3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 15-33844930-G-A is Benign according to our data. Variant chr15-33844930-G-A is described in ClinVar as [Benign]. Clinvar id is 461862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.161 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00882 (1343/152310) while in subpopulation SAS AF= 0.0253 (122/4824). AF 95% confidence interval is 0.0216. There are 11 homozygotes in gnomad4. There are 671 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR3	NM_001036.6 linkuse as main transcript	c.13365G>A	p.Glu4455Glu	synonymous_variant	93/104	ENST00000634891.2	NP_001027.3	Q15413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR3	ENST00000634891.2 linkuse as main transcript	c.13365G>A	p.Glu4455Glu	synonymous_variant	93/104	1	NM_001036.6	ENSP00000489262.1		Q15413-1

Frequencies

GnomAD3 genomes

AF:

0.00883

AC:

1344

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00942

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0255

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0123

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.0113

AC:

2817

AN:

249270

Hom.:

AF XY:

0.0125

AC XY:

1685

AN XY:

135232

show subpopulations

Gnomad AFR exome

AF:

0.00187

Gnomad AMR exome

AF:

0.00765

Gnomad ASJ exome

AF:

0.0243

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0238

Gnomad FIN exome

AF:

0.00446

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0114

AC:

16596

AN:

1461686

Hom.:

131

Cov.:

AF XY:

0.0119

AC XY:

8637

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00170

Gnomad4 AMR exome

AF:

0.00787

Gnomad4 ASJ exome

AF:

0.0228

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0241

Gnomad4 FIN exome

AF:

0.00498

Gnomad4 NFE exome

AF:

0.0112

Gnomad4 OTH exome

AF:

0.0121

GnomAD4 genome

AF:

0.00882

AC:

1343

AN:

152310

Hom.:

Cov.:

AF XY:

0.00901

AC XY:

671

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00200

Gnomad4 AMR

AF:

0.00941

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0253

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.0123

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.00830

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0116

EpiControl

AF:

0.0107

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 15, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

0.69

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over